Modern codes of practice such as Eurocode strive to provide design rules including partial factors with an appropriate level of safety for a wide range of applications. The target reliability levels and partial factors in such codes are not equally efficient for all applications, since they are calibrated to work well in both typical and unusual situations. For large engineered systems like flood defense systems with large potential consequences and substantial investments in improvement and maintenance, it is worthwhile to develop tailor-made solutions. This paper describes the approach adopted in the Netherlands to develop safety requirements to flood defenses such as partial factors for dikes within an acceptable risk framework accounting for system reliability aspects. The main steps herein are to define a risk-informed target reliability for the whole system (i.e., including all elements and failure modes), to derive target reliabilities for specific elements (e.g., dike sections) and failure modes and to calibrate partial factors on the latter. After describing those steps, the paper provides an application example for the uplift and piping failure mode (i.e., internal erosion).